First-in-class HIF-2α inhibitor improves outcomes in patients with previously treated advanced clear cell renal cell carcinoma

Accounting for 2-3% of malignant tumors in adults, renal cell carcinoma (RCC), also known as renal cell adenocarcinoma, is a rare disease originating in the lining of kidney tubules. Clear cell RCC (ccRCC) is the most common type of kidney cancer, representing almost 80% of all cases.

“If detected early, most people with kidney cancer can be cured with surgery. However, the prognosis of metastatic clear cell renal cell carcinoma is poor and identifying new therapies to improve outcomes for patients who are refractory to immunotherapy and VEGF-targeted therapies represents an unmet clinical need,” explains Cristina Suarez, Medical Oncologist at the Vall d’Hebron University Hospital (HUVH), Senior Clinical Investigator of the Vall d’Hebron Institute of Oncology’s (VHIO) Genitourinary, Central Nervous System Tumors and Sarcoma Group, and co-author of the phase III LITESPARK-005 study, results of which were presented today* at the ESMO Congress 2023, 20-24 October in Madrid.

Hypoxia is a common feature of most solid tumors, rendering them more resistant to therapy. Belzutifan is a first-in-class oral inhibitor of hypoxia-inducible factor 2α (HIF-2α) approved in the United States for the treatment of cancers associated with von Hippel-Lindau syndrome, including different types of renal cancer and pancreatic neuroendocrine tumors, among others.

The phase III LITESPARK-005 clinical trial was designed to evaluate belzutifan versus targeted therapy with everolimus in patients with advanced ccRCC who had received prior treatment with immunotherapy and VEGF-targeted therapies. The study included a total of 746 patients who were randomized 1:1 to receive belzutifan or everolimus.

The investigators observed a 25% delay in the time to disease progression in patients treated with belzutifan compared with those patients who received everolimus, with an overall response rate of 21.9% versus 3.5%, respectively. The safety profile of belzutifan was consistent with prior reports, and treatment-related adverse events occurred in 38.7% of patients. Health-related quality of life was maintained for a longer duration in patients receiving belzutifan.

“Results of this study point to HIF-2α blockade with belzutifan as a potential new therapeutic option for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy and VEGF-targeted therapies,” concludes Cristina Suarez, co-Chair of the corresponding ESMO Congress session, along with Manuela Schmidinger, Associate Professor of Medicine and Program Director, Renal Cell Carcinoma at the Medical University of Vienna (MedUni Vienna), Austria.

Abstract reference:

LBA88 – Belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): randomized open-label phase 3 LITESPARK-005 study. Laurence Albiges, Toni K. Choueiri, Katriina Peltola, Guillermo Velasco Oria de Rueda, Mauricio Burotto, Cristina Suarez Rodriguez, Pooja Ghatalia, Roberto Iacovelli, Elaine Lam, Elena Verzoni, Mahmut Gumus, Walter Stadler, Christian Kollmannsberger, Bohuslav Melichar, Balaji Venugopal, Aobo Wang, Rodolfo F. Perini, Donna Vickery, Brian Rini, Thomas Powles.

Session details:

ESMO Congress 2023

20 – 24 October, Madrid, Spain

Session Type: Proffered Paper session 2 – Genitourinary tumours, non-prostate

Date: Saturday, 21 October 2023

Time: 14:45 – 16:10

Chairs: Manuela Schmidinger (Viena, Austria) Cristina Suarez (Barcelona, Spain)

Room: Barcelona Auditorium – Hall 9